2-Benzo[b]thiophenecarboxylic acids and derivatives thereof are useful as intermediates in the manufacture of pharmaceuticals, agricultural chemicals, and in material preservation chemicals. See, e.g., European Patent 0 715 625.
Kolasa et al, Syn. Comm. 23(6): 743-8 (1993), describe an anhydrous process for the preparation of ethyl 2-benzo[b]thiophenecarboxylate by the reaction of 2-nitrobenzaldehyde and ethyl mercaptoglycolate in dimethylformamide (DMF) solvent and anhydrous potassium carbonate.
Zambias et al, Syn. Comm. 21(7): 959-964 (1991), describe a method for the preparation of methyl 2-benzo[b]thiophenecarboxylate which comprises: (1) reacting 2-chloro-5-nitrobenzaldehyde with methyl thioglycolate in methanol at 50-60.degree. C. in the presence of sodium methoxide; and then (2) heating the resultant reaction mixture at reflux in the additional presence of sodium hydroxide.
U.S. Pat. No. 5,298,630 describes a two step process for the preparation of 2-benzo[b]thiophenecarboxylic acid: (1) reacting a 2-halobenzaldehyde with an alkyl mercaptan in the presence of alkali at reflux temperature, preferably using a phase transfer catalyst, to produce a 2-alkylthiobenzaldehyde intermediate; and then (2) treating this intermediate with a 2-haloacetic acid at 110.degree. C. to produce 2-benzo[b]thiophenecarboxylic acid and an alkyl halide by-product.
Japanese Kokai Patent Application JP-05194484 describes a method for the preparation of benzo[b]thiophene-2-carboxylic acid which comprises: (1) reacting a 2-chlorobenzaldehyde with a dialkali salt of 2-mercaptoacetic acid, in an aprotic polar solvent, to produce a 2-[(2-formylphenyl)thio]acetate alkali metal salt intermediate; and then (2) cyclizing the intermediate in the presence of a base, to produce the benzo[b]-thiophene-2-carboxylic acid after neutralization. This method is conducted anhydrously and requires two separate organic solvents.
It is the purpose of this invention to provide a novel process for the preparation of 2-benzo[b]thiophenecarboxylic acid derivatives in an aqueous medium and without an organic solvent.